Data from the phase 2 the phase 3 SWOG S1216 presented during the ASCO Annual Meeting shows numerical overall survival improvement with he experimental combination that missed the threshold for statistical significance.
The use of TAK-700 combined with androgen-deprivation therapy (ADT) demonstrated numerical improvement in overall survival (OS) compared with ADT plus bicalutamide, but the result did not meet the prespecified threshold for statistical significance in patients with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC), according to findings from the phase 3 SWOG S1216 trial presented during the 2021 ASCO Annual Meeting.
Despite missing the primary end point, a posthoc analysis uncovered a pathway for optimizing care in this patient population.
The findings, which were presented at the 2021 ASCO Annual Meeting, showed that at a median follow-up of 4.9 years, the median OS was 81.1 months in the TAK-700 arm versus 70.2 months in the control arm (HR, 0.86; 95% CI, 0.72-1.02; P = .04). This 11+ month improvement in OS did not meet the trial’s prespecified criteria for statistical significance.
The investigators, led by Neeraj Agarwal, MD, conducted a posthoc analysis of the survival data because the median OS of 70.2 months in the control arm was much higher than expected. This OS for bicalutamide was 16 months higher than the investigators anticipated when designing the trial. The study hypothesis was that the control arm would achieve a 54-month median OS, Agarwal, a professor of Medicine at the Huntsman Cancer Institute, explained in an interview with Targeted Oncology.
The posthoc analysis looked at subsequent use of life-prolonging therapies and found that 77% of patients in the control arm had received such treatments, compared with 61% of patients in the TAK-700 arm. “This may have resulted in the 70-month median OS in the control arm, which is the highest ever reported for patients on ADT alone, or in a non-intensified ADT arm, of all contemporary trials in mHSPC,” said Agarwal.
Commenting on the totality of findings from the primary and posthoc analyses, Agarwal said, “Results from SWOG S1216 portend great news for our patients with newly diagnosed mHSPC. These results show that early intensification of ADT in the mHSPC setting in combination with access to life-prolonging therapies in the metastatic castration-resistant prostate cancer setting is likely going to result in unprecedented overall survival benefits in our patients.”
TAK-700 is a specific 17,20-lyase inhibitor that does require steroids. The SWOG S1216 study included 1279 patients who were accrued between March 2013 and July 2017.
Baseline characteristics were well balanced between the study arms. In the TAK-700 arm,
the median age at baseline was 68 years (range, 46-90), the median PSA was 27.2ng/mL (range, 2-6710), 49% of patients had extensive disease, and 10% of patients were Black. Zubrod performance scores were 0 (65%), 1 (31%), 2 (3%), 3 (<1%), and missing (<1%). Gleason scores at initial diagnosis were <7 (7%), 7 (26%), 8 (19%), 9-10 (39%), and missing (9%).
Patients were randomized in a 1:1 ratio to ADT plus either TAK-700 (n = 638; 300 mg twice daily) or bicalutamide (n = 641; 50 mg daily). The primary end point was OS. Key secondary end points included progression-free survival (PFS), PSA response at 7 months, and safety.
PFS and PSA response were significantly improved in the TAK-700 arm. The median PFS was 47.6 months in the TAK-700 arm versus 23 months in the bicalutamide arm, translating to a 42% reduction in the risk of disease progression or death (HR, 0.58; 95% CI, 0.51-0.67; P <.0001).
Regarding PSA response, 58.3% of patients in the TAK-700 arm reached a PSA ≤0.2 ng/ml compared with 44% of patients in the control arm. The PSA level ranged between 0.2 and 4 ng/ml in 22.3% versus 31.4% of the 2 arms, respectively. The PSA nonresponse rates (PSA >4.0 ng/ml) were 19% versus 25%, respectively.
Regarding safety, there were more grade 3/4 adverse events (AEs) in the TAK-700 arm versus the bicalutamide arm at 43% versus 14%, respectively. Of note, rates of grade 3/4 hypertension were 20% versus 5%, and rates of grade 3/4 fatigue were 5% versus 2%, respectively. There were 5 patient deaths in the TAK-700 arm compared with 1 in the control arm.
“It will be key moving forward to offer ADT intensification to all eligible patients. We cannot justify treating our patients with non-intensified ADT anymore. [Patients should receive intensified ADT] and then life-prolonging therapies, which are approved in castration-resistant prostate cancers. If you combine these two, you will see an unprecedented overall survival benefit for patients with newly diagnosed mHSPC,” concluded Agarwal.
SWOG S1216: A phase III randomized trial comparing androgen deprivation therapy (ADT) plus TAK-700 with ADT plus bicalutamide in patients (pts) with newly diagnosed metastatic hormone-sensitive prostate cancer (mHSPC) (NCT01809691). J Clin Oncol 39, 2021 (suppl 15; abstr 5001). doi: 10.1200/JCO.2021.39.15_suppl.5001